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https://www.readbyqxmd.com/read/28919755/synthetic-high-density-lipoprotein-nanodisks-for-targeted-withalongolide-delivery-to-adrenocortical-carcinoma
#1
Rui Kuai, Chitra Subramanian, Peter T White, Barbara N Timmermann, James J Moon, Mark S Cohen, Anna Schwendeman
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy and has a 5-year survival rate of <35%. ACC cells require cholesterol for steroid hormone production, and this requirement is met via expression on the cell surface of a high level of SRB1, responsible for the uptake of high-density lipoproteins (HDLs), which carry and transport cholesterol in vivo. Here, we describe how this natural lipid carrier function of SRB1 can be utilized to improve the tumor-targeted delivery of a novel natural product derivative - withalongolide A 4,19,27-triacetate (WGA-TA) - which has shown potent antitumor efficacy, but poor aqueous solubility...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28917152/pegylated-thermosensitive-lipid-coated-hollow-gold-nanoshells-for-effective-combinational-chemo-photothermal-therapy-of-pancreatic-cancer
#2
Bijay Kumar Poudel, Biki Gupta, Thiruganesh Ramasamy, Raj Kumar Thapa, Shiva Pathak, Kyung Taek Oh, Jee-Heon Jeong, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Pancreatic cancer has extremely poor prognosis with an 85% mortality rate that results from aggressive and asymptomatic growth, high metastatic potential, and rapid development of resistance to already ineffective chemotherapy. In this study, plasmonic hollow gold nanoshells (GNS) coated with PEGylated thermosensitive lipids were prepared as an efficient platform to ratiometrically co-deliver two drugs, bortezomib and gemcitabine (GNS-L/GB), for combinational chemotherapy and photothermal therapy of pancreatic cancer...
September 8, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28912673/improving-the-delivery-of-sod1-antisense-oligonucleotides-to-motor-neurons-using-calcium-phosphate-lipid-nanoparticles
#3
Liyu Chen, Clare Watson, Marco Morsch, Nicholas J Cole, Roger S Chung, Darren N Saunders, Justin J Yerbury, Kara L Vine
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease affecting the upper and lower motor neurons in the motor cortex and spinal cord. Abnormal accumulation of mutant superoxide dismutase I (SOD1) in motor neurons is a pathological hallmark of some forms of the disease. We have shown that the orderly progression of the disease may be explained by misfolded SOD1 cell-to-cell propagation, which is reliant upon its active endogenous synthesis. Reducing the levels of SOD1 is therefore a promising therapeutic approach...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28903183/inhibition-of-hemangioma-growth-using-polymer-lipid-hybrid-nanoparticles-for-delivery-of-rapamycin
#4
Haitao Li, Yunfei Teng, Jin Sun, Jianyong Liu
Although infantile hemangiomas is benign, its rapid growth may induce serious complications. However, only one drug Hemangeol™ has been approved by US Food and Drug Administration (FDA) to treat infantile hemangiomas. Thus it is necessary to develop novel alternative drugs to treat infantile hemangiomas. Rapamycin is a well-know potent antiangiogenic agent, whereas the daily oral administration of rapamycin exerts undesired metabolic effects due to its inhibition of mechanistic target of rapamycin (mTOR) which is critical in cell metabolism...
September 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28900509/biodegradable-hollow-mesoporous-silica-nanoparticles-for-regulating-tumor-microenvironment-and-enhancing-antitumor-efficiency
#5
Miao Kong, Jiamin Tang, Qi Qiao, Tingting Wu, Yan Qi, Songwei Tan, Xueqin Gao, Zhiping Zhang
There is accumulating evidence that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Herein, to remodel tumor immune microenvironment and elicit synergistic antitumor effects, lipid-coated biodegradable hollow mesoporous silica nanoparticle (dHMLB) was constructed with co-encapsulation of all-trans retinoic acid (ATRA), doxorubicin (DOX) and interleukin-2 (IL-2) for chemo-immunotherapy. The nanoparticle-mediated combinational therapy provided a benign regulation on tumor microenvironment through activation of tumor infiltrating T lymphocytes and natural killer cells, promotion of cytokines secretion of IFN-γ and IL-12, and down-regulation of immunosuppressive myeloid-derived suppressor cells, cytokine IL-10 and TGF-β...
2017: Theranostics
https://www.readbyqxmd.com/read/28895754/coenzyme-q10-and-retinaldehyde-co-loaded-nanostructured-lipid-carriers-for-efficacy-evaluation-in-wrinkles
#6
Kritika Nayak, Sameer S Katiyar, Varun Kushwah, Sanyog Jain
The present study depicts coenzyme Q10 (CoQ10) and retinaldehyde (RAL) co-loaded Nanostructured Lipid Carriers (NLCs); having activity on different targets of photoageing, which can overcome deficits of conventional topical dosage forms. The developed NLCs were characterized for particle size, polydispersity index, and % Entrapment efficiency, followed by their incorporation into Carbopol® 934P-NF gel. In vitro cellular uptake and cytotoxicity assay was performed to evaluate NLCs and in vivo study on UV induced wrinkle model to determine efficacy of NLCs...
September 12, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28892872/polymer-lipid-hybrid-nanoparticles-based-paclitaxel-and-etoposide-combinations-for-the-synergistic-anticancer-efficacy-in-osteosarcoma
#7
Rui Duan, Caiyan Li, Fan Wang, Jin-Chu Yangi
In this study, paclitaxel and etoposide-loaded lipid-polymer hybrid nanoparticles (PE-LPN) was successful prepared and evaluated for physicochemical and anticancer effect. Nanosized PE-LPN was obtained with a perfect spherical morphology. PE-LPN exhibited a controlled release of two drugs in a sequential manner. The nanoparticles exhibited a typical endocytosis-mediated cellular uptake in cancer cells. The ratiometric combination of paclitaxel (PTX) and etoposide (ETP) were significantly more cytotoxic than individual drugs...
August 30, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28892400/poly-vinyl-methyl-ether-maleic-anhydride-doped-peg-pla-nanoparticles-for-oral-paclitaxel-delivery-to-improve-bioadhesive-efficiency
#8
Qian Wang, Chan Li, Tianyang Ren, Shizhu Chen, Xiaoxia Ye, Hongbo Guo, Haibing He, Yu Zhang, Tian Yin, Xing-Jie Liang, Xing Tang
Bioadhesive nanoparticles based on PVMMA (poly (vinyl methyl ether/maleic anhydride)) and mPEG-b-PLA (Poly (ethylene glycol) methyl ether - b - poly (D, L - lactic acid)) were produced by the emulsification solvent evaporation method. Paclitaxel was utilized as the model drug, with an encapsulation efficiency of up to 90.2 ± 4.0%. The nanoparticles were uniform and spherical in shape, and exhibited a sustained drug release compared with Taxol®. M-NPs also exhibited favorable bioadhesive efficiency at the same time...
September 11, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28890238/delivering-the-right-message-challenges-and-opportunities-in-lipid-nanoparticles-mediated-modified-mrna-therapeutics-an-innate-immune-system-standpoint
#9
REVIEW
Yasmin Granot, Dan Peer
mRNA molecules hold tremendous potential as a tool for gene therapy of a wide range of diseases. However, the main hurdle in implementation of mRNA for therapeutics, the systemic delivery of mRNA molecules to target cells, remains a challenge. A feasible solution for this challenge relies in the rapidly evolving field of nucleic acid-loaded nanocarriers and specifically in the established family of lipid-based nanoparticles (LNPs). Herein, we will discuss the main factors, which determine the fate of modified mRNA (mmRNA)-loaded LNPs in-vivo, and will focus on their interactions with the innate immune system as a main consideration in the design of lipid-based mmRNA delivery platforms...
September 7, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28889081/distinct-solubility-and-cytotoxicity-regimes-of-paclitaxel-loaded-cationic-liposomes-at-low-and-high-drug-content-revealed-by-kinetic-phase-behavior-and-cancer-cell-viability-studies
#10
Victoria M Steffes, Meena M Murali, Yoonsang Park, Bretton J Fletcher, Kai K Ewert, Cyrus R Safinya
Lipid-based particles are used worldwide in clinical trials as carriers of hydrophobic paclitaxel (PTXL) for cancer chemotherapy, albeit with little improvement over the standard-of-care. Improving efficacy requires an understanding of intramembrane interactions between PTXL and lipids to enhance PTXL solubilization and suppress PTXL phase separation into crystals. We studied the solubility of PTXL in cationic liposomes (CLs) composed of positively charged 2,3-dioleyloxypropyltrimethylammonium chloride (DOTAP) and neutral 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) as a function of PTXL membrane content and its relation to efficacy...
August 17, 2017: Biomaterials
https://www.readbyqxmd.com/read/28883727/vaccination-with-poly-d-l-lactide-co-glycolide-nanoparticles-loaded-with-soluble-leishmania-antigens-and-modified-with-a-tnf%C3%AE-mimicking-peptide-or-monophosphoryl-lipid-a-confers-protection-against-experimental-visceral-leishmaniasis
#11
Maritsa Margaroni, Maria Agallou, Evita Athanasiou, Olga Kammona, Costas Kiparissides, Catherine Gaitanaki, Evdokia Karagouni
Visceral leishmaniasis (VL) persists as a major public health problem, and since the existing chemotherapy is far from satisfactory, development of an effective vaccine emerges as the most appropriate strategy for confronting VL. The development of an effective vaccine relies on the selection of the appropriate antigen and also the right adjuvant and/or delivery vehicle. In the present study, the protective efficacy of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), which were surface-modified with a TNFα-mimicking eight-amino-acid peptide (p8) and further functionalized by encapsulating soluble Leishmania infantum antigens (sLiAg) and monophosphoryl lipid A (MPLA), a TLR4 ligand, was evaluated against challenge with L...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28879687/recombinant-synthesis-of-hybrid-lipid-peptide-polymer-fusions-that-self-assemble-and-encapsulate-hydrophobic-drugs
#12
Kelli M Luginbuhl, Davoud Mozhdehi, Michael Dzuricky, Parisa Yousefpour, Fred C Huang, Nicholas R Mayne, Kristen Buehne, Ashutosh Chilkoti
Inspired by biohybrid molecules that are synthesized in Nature through post-translational modification (PTM), we have exploited a eukaryotic PTM to recombinantly synthesize lipid-polypeptide hybrid materials. By co-expressing yeast N-myristoyltransferase with an elastin-like polypeptide (ELP) fused to a short recognition sequence in E. coli, we show robust and high yield modification of the ELP with myristic acid. The ELP's reversible phase behavior is retained upon myristoylation and can be tuned to span a 30-60 °C...
September 6, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28870072/building-stable-mmp2-responsive-multifunctional-polymeric-micelles-by-an-all-in-one-polymer-lipid-conjugate-for-tumor-targeted-intracellular-drug-delivery
#13
Qing Yao, Zhi Dai, Jong Hoon Choi, Dongin Kim, Lin Zhu
In this study, we described an "all-in-one" polymer-lipid conjugate (PEG2k-ppTAT-PEG1k-PE) that could self-assemble to matrix metalloproteinase 2 (MMP2)-sensitive multifunctional micelles. The assembled micelles had several key features, including a protective long chain polyethylene glycol (PEG2k) (the outer shell), an MMP2-sensitive peptide linker (pp) (the tumor-targeting middle layer), a trans-activating transcriptional activator (TAT) peptide (the cell penetrating middle layer), and a stable PEG1k-PE micelle for drug loading (the inner core)...
September 5, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28869892/combination-lung-cancer-chemotherapy-design-of-a-ph-sensitive-transferrin-peg-hz-lipid-conjugate-for-the-co-delivery-of-docetaxel-and-baicalin
#14
Shuang Li, Lin Wang, Na Li, Yucai Liu, Hui Su
The aim of the present study is to design a novel dual-ligand lipid based nanoparticle system. It is conducted by a specific ligand and pH sensitive lipid conjugate. Docetaxel (DTX) and baicalein (BA) are co-delivered by this system for combination lung cancer chemotherapy. Firstly, transferrin (Tf)-polyethylene glycol (PEG)-hydrazone (hz)-glyceryl monostearate (GMS), Tf-PEG-hz-GMS, was synthesized. Tf decorated DTX and BA loaded solid lipid nanoparticles (Tf-D/B-SLNs) were prepared by emulsification method...
August 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28868334/loading-of-extracellular-vesicles-with-chemically-stabilized-hydrophobic-sirnas-for-the-treatment-of-disease-in-the-central-nervous-system
#15
Reka A Haraszti, Andrew Coles, Neil Aronin, Anastasia Khvorova, Marie-Cécile Didiot
Efficient delivery of oligonucleotide therapeutics, i.e., siRNAs, to the central nervous system represents a significant barrier to their clinical advancement for the treatment of neurological disorders. Small, endogenous extracellular vesicles were shown to be able to transport lipids, proteins and RNA between cells, including neurons. This natural trafficking ability gives extracellular vesicles the potential to be used as delivery vehicles for oligonucleotides, i.e., siRNAs. However, robust and scalable methods for loading of extracellular vesicles with oligonucleotide cargo are lacking...
June 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28866808/chylomicrons-stimulate-incretin-secretion-in-mouse-and-human-cells
#16
Arianna Psichas, Pierre F Larraufie, Deborah A Goldspink, Fiona M Gribble, Frank Reimann
AIMS/HYPOTHESIS: Lipids are a potent stimulus for the secretion of glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic peptide (GIP). Traditionally, this effect was thought to involve the sensing of lipid digestion products by free fatty acid receptor 1 (FFA1) and G-protein coupled receptor 119 (GPR119) on the apical surface of enteroendocrine cells. However, recent evidence suggests that lipids may in fact be sensed basolaterally, and that fatty acid absorption and chylomicron synthesis may be a prerequisite for their stimulatory effect on gut peptide release...
September 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/28866799/intranasal-administration-of-tat-conjugated-lipid-nanocarriers-loading-gdnf-for-parkinson-s-disease
#17
Sara Hernando, Enara Herran, Joana Figueiro-Silva, José Luis Pedraz, Manoli Igartua, Eva Carro, Rosa Maria Hernandez
Parkinson's disease (PD) is the second most common neurodegenerative disorder (ND), characterized by the loss of dopaminergic neurons, microglial activation, and neuroinflammation. Current available treatments in clinical practice cannot halt the progression of the disease. During the last few years, growth factors (GFs) have been raised as a promising therapeutic approach to address the underlying neurodegenerative process. Among others, glial cell-derived neurotrophic factor (GDNF) is a widely studied GF for PD...
September 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28866132/combining-r-dotap-and-a-particulate-antigen-delivery-platform-to-trigger-dendritic-cell-activation-formulation-development-and-in-vitro-interaction-studies
#18
Markus Riehl, Meike Harms, Andrea Hanefeld, Renato B Baleeiro, Peter Walden, Karsten Mäder
The utilization of the cationic lipid R-DOTAP as immune cell stimulant (e.g. its stimulating effects on immature dendritic cells) and correspondingly as possible adjuvant for vaccination is well known. Likewise, it is described in literature that solid polymer particles loaded with antigens can be size-tailored in a manner to be suitable for phagocytosis by antigen presenting cells. The effects of DOTAP-microparticle combinations, however, are not well understood. This study aimed therefore to explore the potential of R-DOTAP stabilized microparticles (MP) to act as a carrier platform for antigens e...
September 1, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28865358/fabrication-of-all-trans-retinoic-acid-loaded-biocompatible-precirol-a-strategy-for-escaping-dose-dependent-side-effects-of-doxorubicin
#19
Mehdi Sabzichi, Jamal Mohammadian, Marjan Ghorbani, Somaiyeh Saghaei, Hadi Chavoshi, Fatemeh Ramezani, Hamed Hamishehkar
BACKGROUND: Drug delivery-based nanoparticles have been emerged to be an alternative and efficient approach to cancer therapy compared to conventional systems. Here, we investigated the role of all-trans retinoic acid (ATRA) formulated with precirol in increasing doxorubicin (Dox) induced apoptosis and cell cycle arrest in MDA-MB-231 breast cancer cells. METHODS: ATRA-loaded Nano structured lipid carriers (NLCs) were evaluated in terms of particle size, zeta potential, Fourier transforms infrared spectroscopy (FTIR), cell internalization, and scanning electron microscope (SEM)...
August 25, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28865342/inclusion-of-oligonucleotide-antimicrobials-in-biocompatible-cationic-liposomes-a-structural-study
#20
Marianna Mamusa, Francesco Barbero, Costanza Montis, Laura Cutillo, Ana Gonzalez-Paredes, Debora Berti
HYPOTHESIS: Transcription factor decoys (TFD) are short oligonucleotides designed to block essential genetic pathways in bacteria and defeat resistant infections. TFD protection in biological fluids and their delivery to the site of infection require formulation in appropriate delivery systems. In this work, we build on a classical phosphatidylcholine/phosphatidylethanolamine (POPC/DOPE) scaffold to design TFD-loaded cationic liposomes by combining the DNA-complexing abilities of a bolaamphiphile, (1,1'-(dodecane-1,12-diyl)-bis-(9-amino-1,2,3,4-tetrahydroacridinium) chloride (12-bis-THA), with the biocompatible cationic lipid ethyl-phosphatidylcholine (DPePC)...
August 24, 2017: Journal of Colloid and Interface Science
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